Effectiveness of Curcumin on Outcomes of Hospitalized COVID-19 Patients: A Systematic Review of Clinical Trials

Despite the ongoing vaccination efforts, there is still an urgent need for safe and effective treatments to help curb the debilitating effects of COVID-19 disease. This systematic review aimed to investigate the efficacy of supplemental curcumin treatment on clinical outcomes and inflammation-related biomarker profiles in COVID-19 patients. We searched PubMed, Scopus, Web of Science, EMBASE, ProQuest, and Ovid databases up to 30 June 2021 to find studies that assessed the effects of curcumin-related compounds in mild to severe COVID-19 patients. Six studies were identified which showed that curcumin supplementation led to a significant decrease in common symptoms, duration of hospitalization and deaths. In addition, all of these studies showed that the intervention led to amelioration of cytokine storm effects thought to be a driving force in severe COVID-19 cases. This was seen as a significant (p < 0.05) decrease in proinflammatory cytokines such as IL1β and IL6, with a concomitant significant (p < 0.05) increase in anti-inflammatory cytokines, including IL-10, IL-35 and TGF-α. Taken together, these findings suggested that curcumin exerts its beneficial effects through at least partial restoration of pro-inflammatory/anti-inflammatory balance. In conclusion, curcumin supplementation may offer an efficacious and safe option for improving COVID-19 disease outcomes. We highlight the point that future clinical studies of COVID-19 disease should employ larger cohorts of patients in different clinical settings with standardized preparations of curcumin-related compounds.

NITRO CELLULOSE POWDER CHARGES OF LONG SERVICE LIFE: PROBLEMS AND THEIR POSSIBLE SOLUTIONS

One of the components of the problem of Ukraine's national security is the loading of warehouses with a variety of ammunition with an expired guaranteed storage period. The experience of storing ammunition shows that during long-term storage, propylene powder used in ammunition is capable of spontaneously undergoing various physical and chemical transformations, which negatively affects the ballistic characteristics of ammunition. The lack of ammunition production in Ukraine has led to the fact that ammunition is currently in operation, the storage time of which reaches 25-30 years or more. This article analyzes publications devoted to scientific research related to the problems of ballistic stability of propellants. A number of factors are presented that affect the physicochemical stability of powder charges during their long-term operation. The generalizing data on changes in the main ballistic characteristics of ammunition at different periods of their storage are presented. It is assumed that one of the ways to improve the ballistic and energy characteristics of ammunition with long service lives can be the regeneration of nitrocellulose powder charges. It is shown that at present there are no methods for the regeneration of propellant charges of long service life. However, there are encouraging data on the treatment of propellants with hydrogen peroxide, on the basis of which a technology can be developed for the complete or partial restoration of the ballistic and energy characteristics of the propellant charge. It is presented that the predictive assessment of changes in the characteristics of ammunition with long service lives does not correspond to their real indicators. It has been determined that the problem of nitrocellulose propellants of long service life is complex and, on the basis of its solution, theoretical and methodological foundations of the regeneration of nitrocellulose propellant charges can be developed to homologate the ballistic and energy characteristics of ammunition.

Stem Cell Therapy Enhances Motor Activity of Triceps Surae Muscle in Mice with Hereditary Peripheral Neuropathy

Impaired motor and sensory functions are the main features of Charcot–Marie–Tooth disease. Mesenchymal stem cell (MSCs) therapy is one of the possible treatments for this disease. It was assumed that MSCs therapy can improve the contractile properties of the triceps surae (TS) muscles in mice with hereditary peripheral neuropathy. Murine adipose-derived mesenchymal stromal cells (AD-MSCs) were obtained for transplantation into TS muscles of FVB-C-Tg(GFPU)5Nagy/J mice. Three months after AD-MSCs transplantation, animals were subjected to electrophysiological investigations. Parameters of TS muscle tension after intermittent high frequency electrical sciatic nerve stimulations were analyzed. It was found that force of TS muscle tension contraction in animals after AD-MSCs treatment was two-time higher than in untreated mice. Normalized values of force muscle contraction in different phases of electrical stimulation were 0.3 ± 0.01 vs. 0.18 ± 0.01 and 0.26 ± 0.03 vs. 0.13 ± 0.03 for treated and untreated animals, respectively. It is assumed that the two-fold increase in TS muscle strength was caused by stem cell therapy. Apparently, AD-MSCs therapy can promote nerve regeneration and partial restoration of muscle function, and thus can be a potential therapeutic agent for the treatment of peripheral neuropathies.

Progress in Gene Editing Tools and Their Potential for Correcting Mutations Underlying Hearing and Vision Loss

Blindness and deafness are the most frequent sensory disorders in humans. Whatever their cause — genetic, environmental, or due to toxic agents, or aging — the deterioration of these senses is often linked to irreversible damage to the light-sensing photoreceptor cells (blindness) and/or the mechanosensitive hair cells (deafness). Efforts are increasingly focused on preventing disease progression by correcting or replacing the blindness and deafness-causal pathogenic alleles. In recent years, gene replacement therapies for rare monogenic disorders of the retina have given positive results, leading to the marketing of the first gene therapy product for a form of childhood hereditary blindness. Promising results, with a partial restoration of auditory function, have also been reported in preclinical models of human deafness. Silencing approaches, including antisense oligonucleotides, adeno-associated virus (AAV)–mediated microRNA delivery, and genome-editing approaches have also been applied to various genetic forms of blindness and deafness The discovery of new DNA- and RNA-based CRISPR/Cas nucleases, and the new generations of base, prime, and RNA editors offers new possibilities for directly repairing point mutations and therapeutically restoring gene function. Thanks to easy access and immune-privilege status of self-contained compartments, the eye and the ear continue to be at the forefront of developing therapies for genetic diseases. Here, we review the ongoing applications and achievements of this new class of emerging therapeutics in the sensory organs of vision and hearing, highlighting the challenges ahead and the solutions to be overcome for their successful therapeutic application in vivo.

How far to build it before they come? Analyzing the use of the Field of Dreams hypothesis in bull kelp restoration

In restoration ecology, the Field of Dreams Hypothesis posits that restoration efforts that create a suitable environment could lead to eventual recovery of the remaining aspects of the ecosystem through natural processes. Natural processes following partial restoration has lead to ecosystem recovery in both terrestrial and aquatic systems. However, understanding the efficacy of a "field of dreams" approach requires comparison of different approaches to partial restoration in terms of spatial, temporal, and ecological scale to what would happen with more comprehensive restoration efforts. We explore the relative effect of partial restoration and ongoing recovery on restoration efficacy with a dynamical model based on temperate rocky reefs in Northern California. We analyze our model for both the ability and rate of bull kelp forest recovery under different restoration strategies. We compare the efficacy of a partial restoration approach with a more comprehensive restoration effort by exploring how kelp recovery likelihood and rate change with varying intensities of urchin removal and kelp outplanting over different time periods and spatial scales. We find that, for the case of bull kelp forests, setting more favorable initial conditions for kelp recovery through implementing both urchin harvesting and kelp outplanting at the start of the restoration project has a bigger impact on the kelp recovery rate than applying restoration efforts through a longer period of time. Therefore partial restoration efforts, in terms of spatial and temporal scale, can be significantly more effective when applied across multiple ecological scales in terms of both the capacity and rate of achieving the target outcomes.

Asxl1loss cooperates with oncogenic Nras in mice to reprogram immune microenvironment and drive leukemic transformation

Mutations in chromatin regulator ASXL1 are frequently identified in myeloid malignancies, in particular ~40% in chronic myelomonocytic leukemia (CMML). ASXL1 mutations associate with poor prognosis in CMML and significantly co-occur with NRAS mutations. Here, we show that concurrent ASXL1 and NRAS mutations defined a population of CMML patients with shorter leukemia-free survival than those with ASXL1 mutation only. Corroborating this human data, Asxl1-/- accelerated CMML progression and promoted CMML transformation to acute myeloid leukemia (AML) in NrasG12D/+ mice. NrasG12D/+; Asxl1-/- (NA) leukemia cells displayed hyperactivation of MEK/ERK signaling, increased global level of H3K27ac, and Flt3 upregulation. Moreover, we find that NA-AML cells overexpressed all the major inhibitory immune checkpoint ligands, PD-L1/L2, CD155, and CD80/86. Among them, overexpression of PD-L1 and CD86 correlated with upregulation of AP-1 transcription factors (TFs) in NA-AML cells. An AP-1 inhibitor or shRNAs against AP-1 TF Jun decreased PD-L1 and CD86 expression in NA-AML cells. Once NA-AML cells were transplanted into syngeneic recipients, NA-derived T cells were not detectable. Host-derived wildtype T cells overexpressed PD-1 and TIGIT receptors, leading to a predominant exhausted T cell phenotype. Combined inhibition of MEK and BET led to downregulation of Flt3 and AP-1 expression, partial restoration of the immune microenvironment, enhancement of CD8+ T cell cytotoxicity, and prolonged survival in NA-AML mice. Our study suggests that combined targeted therapy and immunotherapy may be beneficial for treating secondary AML with concurrent ASXL1 and NRAS mutations.

Altering the Binding Properties of PRDM9 Partially Restores Fertility across the Species Boundary

Sterility or subfertility of male hybrid offspring is commonly observed. This phenomenon contributes to reproductive barriers between the parental populations, an early step in the process of speciation. One frequent cause of such infertility is a failure of proper chromosome pairing during male meiosis. In subspecies of the house mouse, the likelihood of successful chromosome synapsis is improved by the binding of the histone methyltransferase PRDM9 to both chromosome homologs at matching positions. Using genetic manipulation, we altered PRDM9 binding to occur more often at matched sites, and find that chromosome pairing defects can be rescued, not only in an intersubspecific cross, but also between distinct species. Using different engineered variants, we demonstrate a quantitative link between the degree of matched homolog binding, chromosome synapsis, and rescue of fertility in hybrids between Mus musculus and Mus spretus. The resulting partial restoration of fertility reveals additional mechanisms at play that act to lock-in the reproductive isolation between these two species.

Improvement of Medical Treatment Options of Proximal Deep Vein Thrombosis of Low Extremities Associated with Phlegmasia Alba Dolens

The aim of the study was to improve the conservative treatment options for proximal deep vein thrombosis of low extremities associated with phlegmasia alba dolens optimization of anticoagulant therapy and paravascular injection of the anti-inflammatory medical mixture in areas of the most intense inflammatory process.Materials and methods. The results of treatment of two statistically homogeneous groups of patients with proximal deep vein thrombosis of the lower extremities associated with white phlegmasia were compared. In the first group (n = 30), standard conservative treatment was carried out using rivaroxaban as an anticoagulant; in the second group (n = 30), initial heparin therapy was first performed and, additionally, the following mixture was administered in the places of the greatest severity of inflammatory process under ultrasound control: dexamethasone 16 mg, heparin 5 thousand units, 0.25% novocaine solution 20.0 ml. During treatment the incidence of hemorrhagic syndrome was recorded. The results were assessed after one year according to the degree of deep vein lumen restoration and the severity of venous outflow impairment according to the Villalta scale. Results. In patients of both groups, every tenth patient developed some minor manifestations of hemorrhagic syndrome during treatment with rivaroxaban that was corrected by a decrease in the dose of anticoagulant.Complete restoration of the lumen of the veins occurred in 20.0%, patients of the first group and in 40.0%, patients of the second group; partial, in 63.3% and 56.7% of patients, respectively, minimal - in 16.7% and 3.3% of patients, respectively.In the first group, clinical disorders of venous outflow were absent in 20.0% of patients, a weak degree of severity was registered in 23.3%, an average - in 40.0%, and a strong one in 16.7% of patients, and in the second group, in 40 %, 26.7%, 30% and 3.3% of patients, respectively.Different minor hemorrhagic complications after Rivaroxaban intake occurred equally in both groups in each of ten patients. These complications were treated by the reduction of the anticoagulants dose.Complete restoration of the vein lumen occurred in the first group in 20.0%, and in the second group in 40.0% of patients, partial restoration, in 63.3% and 56.7% of patients, minimal - in 16.7% and 3.3% of patients respectively.In patients of the first group clinical venous congestion was absent in 20,0% of patients, mild congestion was manifested in 23,3% of patients, moderate - in 40,0% of patients, and severe was in 16,7% of cases. In the second group, the obtained data was 40%, 26,7%, 30%, and 3,3% of patients, respectively. Conclusion. Starting therapy with heparin and paravascular injection of anti-inflammatory mixture helps improve treatment outcomes.